Platelet microparticles are not created equal.

In this issue of Blood, Boudreau et al report that activated platelets release respiratory-competent mitochondria either as free organelles or packed in platelet microparticles. Secreted phospholipase A2 IIA hydrolyzes the membrane of these free mitochondria to generate proinflammatory mediators. Results from this study are important in 3 key aspects. First, the authors show that activated platelets produced 3 types of particles: free mitochondria, microparticles containing mitochondria, and mitochondrion-free microparticles. They further show that both free mitochondria and mitochondria packed in microparticles remained active in the respiratory reaction, but the latter required the plasma membrane to be permeabilized by a detergent. The presence and biological activities of cellular microparticles have been recognized for decades, but morphological, structural, and biological characteristics of these subcellular vesicles remain poorly defined and, in some incidences, controversial. Microparticles are currently defined as membrane-bound cellular fragments produced from the plasma membrane of cells that are activated or undergo apoptosis. They are primarily composed of the plasma membrane along with a limited amount of cytoplasm, varying from 0.1 to 1 mm in diameter. A subclass of microparticles is the exosome, which is smaller (50-100 nm) and is derived from granule-containing vesicular bodies. Free mitochondria structurally fit in the definition of exosomes. Microparticles have long been considered as the source and carrier of active molecules that are inflammatory, proproliferation, and proangiogenesis. They also have a unique ability to deliver these active molecules to specific targets through receptors and counterreceptors selectively expressed on them. The current study provides direct evidence that platelet microparticles are heterogeneous not only in size and, perhaps, targeting, but also in biological activities depending on the cargo they carry. Free mitochondria reported in this study can be particularly active in inducing oxidative reactions and, as discussed in the next section, catalytically releasing inflammatory lipid Schematic summary of the biological activities of platelet mitochondria. See Figure 7D in the article by Boudreau et al that begins on page 2173.